National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Biochem Biophys Res Commun. 2010 Oct 22;401(3):401-5. doi: 10.1016/j.bbrc.2010.09.066. Epub 2010 Sep 19.
Human DNA Topoisomerase IIβ binding protein 1 (TopBP1) is a modulating protein that plays an essential role in the response to DNA damage. The N-terminal region of TopBP1, which contains predicted BRCA1-carboxy terminal (BRCT) domains 1 and 2, binds to Rad9, a component of the cell cycle checkpoint clamp Rad9-Hus1-Rad1 complex. Here, we report the crystal structure of the TopBP1N-terminal region (residues 1-290) at 2.4Å resolution. Interestingly, in addition to the predicted tandem BRCT1-2 repeats (residues 103-284), residues 7-98 form a previously unreported BRCT domain (here, BRCT0). In contrast to both BRCT1 and BRCT2, which possess the conventional phosphopeptide binding residues within a surface pocket, the corresponding pocket in BRCT0 is largely hydrophobic. Structural comparisons together with peptide binding studies indicate that the tandem BRCT1-2 domains are the binding region for phosphorylated Ser387 in Rad9.
人类 DNA 拓扑异构酶 IIβ 结合蛋白 1（TopBP1）是一种调节蛋白，在 DNA 损伤反应中发挥着重要作用。TopBP1 的 N 端区域包含两个预测的 BRCA1 羧基末端（BRCT）结构域 1 和 2，与 Rad9 结合，Rad9 是细胞周期检验点 clamp Rad9-Hus1-Rad1 复合物的一个组成部分。在此，我们报道了 TopBP1N 端区域（残基 1-290）在 2.4Å 分辨率下的晶体结构。有趣的是，除了预测的串联 BRCT1-2 重复序列（残基 103-284）外，残基 7-98 还形成了一个以前未报道的 BRCT 结构域（这里称为 BRCT0）。与具有表面口袋内传统磷酸肽结合残基的 BRCT1 和 BRCT2 不同，BRCT0 中的相应口袋主要是疏水性的。结构比较和肽结合研究表明，串联 BRCT1-2 结构域是 Rad9 中磷酸化 Ser387 的结合区域。
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